The overall goal of my research is to elucidate the molecular mechanisms involved in the formation and maintenance of the temporomandibular joint (TMJ), a highly specialized synovial joint found only in mammals. Presently, there is a lack of information about the molecular signals participating in these processes. Previous studies in the limb have indicated that regulatory genes controlling the formation of synovial joints are highly conserved among vertebrates. Studies included in this proposal are based on the hypothesis that "the basic genetic mechanisms regulating synovial joint development are conserved, but TMJ specific genes are also involved during TMJ formation". I will pursue three specific aims: in Aim 1 I will detail the stages of TMJ development in the mouse and investigate the presence of a well-defined group of regulatory genes known to control synovial joint formation in the limb; in Aim 2, I will identify specific regulators and biological markers of TMJ morphogenesis using a high density microarray approach; and in Aim 3, I will test the relevance of these candidate regulatory genes as mediators of TMJ morphogenesis using in vivo approaches. Collectively, these studies aim to close the current knowledge gap on the biology of the TMJ, a fundamental step toward designing novel therapeutic approaches for temporomandibular joint disorders, a significant health problem affecting approximately 12% of the U.S. population. [unreadable] [unreadable] [unreadable]